Stabilized thiamin



Patented Feb; 21, 1950 UNITEDSTATES PATENT 0FFlCE s'rammzan 'rmamm Malcolm u. may. Noblesvllle, ma, assignor to Eli Lilly and Company, Indianapolis, Ind., a corporation of Indiana No Drawing. Application August 27, ms.

' sex-Inigo. 46,561

i i This invention relates to the stabilization of vitamin solutions and to therapeutically useful 0 Claims. (01. 167-81) stable aqueous solutions containing vitamin B1.

The preparation of therapeutically useful aqueous solutions containing vitamin B1, 1. e. thiamin chloride and the like, which have an extended shelf life, which are capable of retaining their full po- -degradative changes, particularly when the thiamin is packaged and supplied to the trade, are obvious.

Attempts have been made to overcome the occurrence of these degradative changes. Thus it has been recommended that only thiamin of the precautions, however, have been only partially successful and have left much to be desired m the provision of solutions of thiamin which will remain substantially colorless and free from any precipitate. Consequently, the loss in potency and the formation of a precipitate in the solutions, which have had no satisfactory explanation, remain as a continual hazard which the art would like to avoid.

An object of my invention is to provide therapeutic solutions comprising stable vitamin B1- containing compositions which do not develop a color or form a precipitate even when stored under adverse conditions of light and heat. Another object is to provide solutions capable of being sterilized by heat without enhancing the tendency of the solution to form a color or precipitate. Other objects will become apparent from the following description of my invention."

In pursuance of the above and other objects,. I have discovered that a stable, aqueous solution f containing thiamin can be obtained by incorporat-" in: in said solution a relatively small amount of so a stabilizing agent of the class consisting'cf thioglycerol, thiosorbitol and thioglucose. A solution containing vitamin B1 and one or more of the stabilizers mentioned above is-stable over long periods of time, can be stored under adverse conditions of heat and light, can be heat-sterilized, and does not require careful exclusion of air during the course of its preparation,

Effectively stabilized aqueous solutions of thia- "in may be obtained by the incorporation of the stabilizing agent in the thiamin solution in a concentration of about 0.5 percent on a weightvolume basis. The practical absence of toxicity of the stabilizing agents employed for the purposes of my invention permits their use in much greater concentration than that specified above, for example, a concentration up to 5.0 per cent may be used. In general there is no particular advantage to be gained by the use of high concentrations. The effectiveness of the stabilizing agents is so great that I have found concentrations as low as 0.03 percent on a weight-volume basis to be fully effective in providing adequate stabilization of aqueous thiamin solutions containing about 0.1 percent thiamin on a weight-volume basis.

In preparing the compositions of my invention it is desirable to provide an aqueous solution containing the selected stabilizing agent in proper concentration, and to add the required amount of thiamin to this solution. By providing a solution in which the stabilizing agent is already present. the decomposition of the thiamin is inhibited from the moment of its solution.

The following examples of therapeutic compositions further illustrate my invention.

Examplei A composition suitable for parenteral administration, comprising the following ingredients:

Thiamin hydrochloride mg 10 Thioglycerol me 5 Water, q. s. ml 1 of comparison, a solution containing 10 m8. of

thiamin per ml. or water, after subjection to the same adverse conditions, became brownish in color and contained a voluminous precipitate.

Example 2 A composition suitable for parenteral use is obtained by employing the following ingredients in the amounts shown below and dissolving them in the order in which they appear:

Water 1 g Thiosorbitol I 50 Thiamin hydrochloride g 40 Nicotinamide 750 Riboflavin g 20 Calcium pantothenate ..g... 50 Pyridoxin hydrochloride g 50 water, q. s. l 10 The composition thus obtained is stable over a long period of time and although initially somewhat yellowish because of the presence 0! riboflavin, it does not develop im'ther color or a precipitate on long standing.

Example 3 A composition embodying several vitamins and suitable for oral administration is as follows:

Aqueous solutions of thiamin prepared for parenteral therapeutic application preferably are slightly acid in order to avoid the known degradation of thi which occurs in the pres- "genee of alkali. Thus it has been the practice to market therapeutic solutions having a pH between about pH 3 and about pH 4, this PH range representing a compromise between a higher pH which causes less pain on iniection and a lower pH at which thiamln is more stable. The stabilized aqueous solutions of thiamin prepared in accordance with my invention are not limitedtothisrangebutarestabieoverawido range. Thus, for example, I have found that even at pH 8 there is no formation of the undesirable precipitate which readily forms in unstabilized solutions at this p8. However, I prefer to prepare thiamin compositions havin: a PH in the range of 2.5 to about 5.

I claim:

l. A solution comprising water, thiamin, and in an amount eilective to stabilise the thiamin. a member of the group consisting of thioglycerol. thiosorbitol and thioglucoee.

2. A solution comprising water. a therapeutically eflective amount of thiamin and. on a weightvoiume basis, from about 0.05 to about 5.0 percent of a member of the group consisting of thioglycerol. thiosorbitol and thioglucose.

3. A therapeutic comtion comprising a solution in an aqueous solvent oi thiamin and, on a weight-volume basis, between 0.05 and 5.0 percent oi a member of the group cc of thioglycerol, thiosorbltol and thioglucose.

4. A composition according to claim 3 containing thioglucose.

5. A composition according to claim 8 containing thioglycerol.

6. A composition according to claim 3 containing thiosorbitol.

MALCOLM D. BRAY.

REFERENCES The following references are of record in the file of this patent: I

UNITED STATES PATENTS Number Name Date 2,047,144 I r: h 31113 7, 1938 so 2,218,592 Taylor Oct. 32, 1940 June i, 1948 

1. A SOLUTION COMPRISING WATER, THIAMIN, AND IN AN AMOUNT EFFECTIVE TO STABILIZE THE THIAMIN, A MEMBER OF THE GROUP CONSISTING OF THIOGLYCEROL, THIOSORBITOL AND THIOGLUCOSE. 